The goals of this proposal are to translate immunologic discoveries from Dr. Carson's laboratory into clinical trials for cancer patients and to use this research program as a means of training young physicians in patient-oriented research. Some of the most exciting new anti-cancer therapies are based on immunologic discoveries. Recombinant cytokines and monoclonal antibodies are now routinely used to treat cancer patients. Dr. Carson's clinical program has focused on two specific areas of investigation: 1). The use of immunostimulatory compounds to augment the immune response to therapeutic anti-tumor monoclonal antibodies, and 2). The use of cytokines alone or in combination with targeted agents to treat patients with metastatic melanoma. The majority of the trials presented here have evolved from basic experimental observations that were made in Dr. Carson's immunology laboratory. Dr. Carson's trials are unique in that they incorporate a series of in-depth correlative studies designed to evaluate the effects of the treatment regimen on the activity of the patient's immune system and the growth of the patient's tumor. These laboratory studies have permitted a rational evaluation of the immunotherapeutic regimens and have guided the development of subsequent trials. In addition, they have allowed Dr. Carson to attract funding for his clinical research from the NCI and other extramural sources. In conjunction with these clinical activities, Dr. Carson has developed a systematic training program in patient-oriented research for young investigators. A number of Medical and Surgical Oncology Fellows, surgical residents, and early career Assistant Professors at the Ohio State University Comprehensive Cancer Center have participated in the development and conduct of Dr. Carson's clinical trials. The goal of this program is to teach participants how to generate and administer protocols of their own design via direct patient interaction and specialized tutorial sessions. Trainees will also attend a series of oncologic didactic sessions and meet regularly with Dr. Carson to discuss their patients and their educational experiences. Dr. Carson's role as national P.I. on a randomized trial of chemotherapy with or without an anti-angiogenic drug (bevacizumab, Avastin(tm)) insures that trainees will also gain valuable experience in this aspect of clinical research. Finally, a special emphasis has been placed on instruction relating to the ethical conduct of patient-oriented research.